Hemodialysis is conventionally instituted in patients with, for example, renal failure. When one suffers from renal failure, various toxins which are normally excreted in the urine are accumulated in the body and the excess water retained due to a decrease in urine volume leads to unbalance of electrolytes in the body fluid so that various signs of acidosis tend to appear. Therefore, a hemodialysis equipment provided with an artificial kidney (dialyzer) is employed to briny the blood into contact with a dialysate through the semipermeable membrane of the dialyzer to remove the uremic toxin and excess water and thereby normalize the electrolytes and improve signs of acidosis.
The hemodialysis equipment used for this purpose varies in scale ranging from a personal or individual equipment designed for hemodialysis of a single individual to a multiple-patient hemodialysis equipment for the concurrent hemodialysis of tens of patients Generally, however, any hemodialysis equipment is a system comprising the following principal components.
(1) a patient monitor (also termed "bedside console"), to which an artificial kidney (dialyzer) comprising A hollow fiber semipermeable membrane is connected; PA1 (2) a dialysate supply unit (also termed "central") which dilutes dialysate A and dialysate B stock solutions with purified water to prepare a dialysate and feeds the prepared dialysate to said patient monitor; PA1 (3) a pipeline system interconnecting said patient monitor and dialysate supply unit; PA1 (4) a water treatment unit comprising a cartridge filter, an activated carbon filter, a soft water-making device, a reverse osmosis unit (RO unit) and the like which prepares a pure diluont water from tap water for the preparation of said dialysate; and PA1 (5) a tank for each of said dialysate A stock solution and dialysate B stock solution for the preparation of said dialysale.
Said dialysate A stock solution generally comprises calcium ion and magnesium ion sources, and typically comprises sodium chloride, potassium chloride, calcium chloride, magnesium chloride, sodium acetate, glucose and the like in a high concentration. Said dialysate B stock solution is generally an aqueous solution of sodium bicarbonate.
Among the above components of hemodialysis equipment, particularly the dialysate B stock solution tank is opened and closed for introduction of the solvent for dialysate B and preparation of dialysate B stock solution, and should hold the solution throughout the hemodialysis session of the day. Moreover, the concentration of, for example, sodium bicarbonate is low. For these reasons, the system is liable to pick up falling bacteria and other microorganisms, with the result that the pipeline within said dialysate supply unit, the dialysate supply line system, and the dialysate line in said patient monitor, among others, are liable to become contaminated with bacteria and endotoxins.
The dialysate supply unit, dialysate supply line system, and the internal dialysate line of the patient monitor are used repeatedly for a long time and the regions of stagnant flow and precipitated carbonate (calcium carbonate) deposits within the lines serve as favorite habitats for bacteria and production of endotoxins, and the contaminated lines favor a further proliferation of bacteria. Moreover, the intra-pipeline fouling with the low molecular weight proteins removed by a high performance membrane dialyzer has recently been pointed out.
Meanwhile, the pure water (generally known as "RO processed water") prepared using an RO membrane such as one used in reverse osmosis apparatus is stored in a hermetically closed RO processed water tank where it is warmed, degassed, used for diluting dialysate stock solutions, for rinse before and after each hemodialysis session, and for dilution of a cleaning disinfectant (cleaning agent), but since it is chlorine-free water, bacteria and endotoxins tend to multiply owing to convection of RO processed water and injury of the RO membrane.
Moreover, since dialysate A stock solution is a high concentration solution containing a small amount of acid, it was formerly believed to be free of bacteria and endotoxins. Actually, however, because the tank is frequently opened and closed, the possibility of contamination has recently been pointed out.
The endotoxins mentioned above exist in the outer cell wall layer of gram-negative bacteria, particularly gram-negative bacilli, and is a lipopolysaccharide (LPS) composed of hydrophilic polysaccharides and hydrophobic lipid A. The endotoxin has activity to induce a variety of humoral factors such as interleukin-1 (IL-1), tumor necrosis factor (TNF) and interferons (IFN), pyrogenicity, fatal toxicity, and activity to cause tissue necrosis, and is omnipresent, for example in tap water, atmospheric air, etc. and on hands and articles.
Dialysis patients show a high positive rate for anti-endotoxin antibodies. Moreover, since the production of IL-1 is more liable in dialysis patients, it is essential to insure that the dialysate and dialysato lines (dialysate circuit) be endotoxin-free.
Furthermore, with the recent use of high performance membranes or highly permeable membranes in clinical practice, back filtration or back diffusion during hemodialysis tends to introduce pyrogens into the patient's blood to cause fever and other adverse reactions in the patient, thus presenting a major clinical problem. It is considered that endotoxins are the most active and most frequent of all pyrogens.
Since multiplication of bacteria and production of large amounts of endotoxins exert adverse effects on the patient, it is a conventional practice to clean and disinfect the dialysis equipment or dialysis machine with a chemical agent such as sodium hypochlorite, acetic acid and/or formalin after the daily dialysis session.
Moreover, with the recent popularity of bicarbonate-containing dialysates, precipitation of the carbonate (calcium carbonate) in the dialysate circuit tends to cause a trouble in the patient monitor, and in order to remove such carbonate deposits, the circuit is generally washed with an acid such as glacial acetic acid, hydrochloric acid or citric acid.
These conventional cleaning disinfectants are more or less satisfactory for disinfection purposes, but because they are highly toxic, these substances must be thoroughly rinsed off with water after use. This rinse procedure requires a large volume of water.
Furthermore, certain conventional cleaning and disinfecting agents such as sodium hypochlorite and formalin have irritating odors and interfere with the cleaning operation, and may cause a stinging pain or ill effects on the mucosa.
Furthermore, the conventional routine cleaning and disinfecting procedure is not sufficiently effective to remove or inactivate endotoxins, and the endotoxin concentration undergoes a progressive increase as the dialysate flows through the dialysis system so that it is frequently found that there is substantially no disparity between the endotoxin concentration in the patient monitor and the endotoxin concentration in tap water.
To avoid such adverse effecLs or endotoxins, a reverse osmosis membrane (RO membrane) is generally used in the water treatment unit for removing endotoxins from tap water. Although endotoxins in tap water can be eliminated by such a water treatment unit, the disinfectant chlorine contained in tap water is also eliminated at the same time so that even when the water purified by an RO membrane (RO processed water) is used for the preparation of a dialysate, the dialysate is sometimes subject to the influence of bacteria.
Meanwhile, filters for removing endotoxins have also been developed and proved to be effective to a certain degree but the installation of such an endotoxin filter introduces other problems such as increased initial cost, complication of the dialysis system, and aging of the filter through adsorption of endotoxins.